Godbole Dhanashri, Mojamdar Manoj, Pal Jayanta K
Cell and Molecular Biology Research Laboratory, Department of Biotechnology, University of Pune, Ganeshkhind, Pune 411 007, Maharastra, India.
Cell Biol Int. 2006 Nov;30(11):895-902. doi: 10.1016/j.cellbi.2006.06.009. Epub 2006 Jun 30.
Proteasomes have been shown to be involved in the regulation of melanin biosynthesis in melanoma cells. Here we report on the correlation between proteasome subunits and Tyrosinase (Tyr) activity in different cell phenotypes, and thereby regulation of melanin biosynthesis in B16F10 mouse melanoma cells. Our results indicated that the quantity of proteasome subunit p27 is higher and that of the enzyme Tyr and its activity are lower in amelanotic melanoma cells, while the reverse is true in melanotic melanoma cells. Proteasome subunit p27, compared to another subunit p31, shows increased co-localization with Tyr and Tyrosinase related protein 1 (Trp1) in amelanotic cells to a greater extent than that in melanotic cells. On exposure to cycloheximide, increased Tyr degradation was seen in amelanotic cells, as indicated by increased co-localization of p27 and Tyr. Further, exposure of amelanotic melanoma cells with proteasome-specific inhibitor MG132 resulted in an increased Tyr activity, increased levels of Tyr and Trp1, leading to increased melanin synthesis. These results therefore suggest that proteasomes, particularly p27 subunit, are directly involved in the regulation of melanin biosynthesis in mouse melanoma cells.
蛋白酶体已被证明参与黑色素瘤细胞中黑色素生物合成的调控。在此，我们报告了蛋白酶体亚基与不同细胞表型中酪氨酸酶（Tyr）活性之间的相关性，从而揭示了B16F10小鼠黑色素瘤细胞中黑色素生物合成的调控机制。我们的结果表明，无黑色素的黑色素瘤细胞中蛋白酶体亚基p27的数量较高，而酪氨酸酶及其活性较低，而有黑色素的黑色素瘤细胞中情况则相反。与另一个亚基p31相比，蛋白酶体亚基p27在无黑色素细胞中与酪氨酸酶和酪氨酸酶相关蛋白1（Trp1）的共定位增加程度大于有黑色素细胞。用环己酰亚胺处理后，无黑色素细胞中酪氨酸酶降解增加，这表现为p27与酪氨酸酶的共定位增加。此外，用蛋白酶体特异性抑制剂MG132处理无黑色素的黑色素瘤细胞会导致酪氨酸酶活性增加、酪氨酸酶和Trp1水平升高，进而导致黑色素合成增加。因此，这些结果表明蛋白酶体，特别是p27亚基，直接参与小鼠黑色素瘤细胞中黑色素生物合成的调控。
